The skin forms a thin sebaceous membrane on the surface of the epidermis. The sebaceous membrane plays the roles of preventing entry of outer foreign matters, protecting the skin against stimulation by various materials, smoothing the surface of the skin, inhibiting water evaporation, etc. However, it is known that excessive sebum is responsible for seborrheic diseases such as acne and dandruff. It is also known that sebum produces peroxides responsible for skin stimulation in the presence of UV rays or the like.
Acne is a typical seborrheic disease that is a skin disease mostly affecting teenagers and scientifically called acne vulgaris. It is clinically defined as “chronic inflammatory lesion prevailing the pilosebaceous systems”. Acne has not been etiologically explained yet, but it is considered as a skin disease caused by complex combination of various factors, among which excessive sebum production, keratinization at the follicle and follicular bacteria are generally thought to have important roles (for example, Yamamoto Ayako: “Guidelines for Current Therapy, 1994 (Volume 36)”, p. 632, Igaku-Shoin, Tokyo (1994)). Thus, common remedies for acne are external preparations containing sebum production inhibitors, keratolytic agents, antibacterials, lipase inhibitors and the like depending on the causative factor. However, acne remedies containing existing active ingredients have various disadvantages. For example, female hormones having a sebum production inhibitory effect inhibit epidermal growth to decrease sebum production, but hormone preparations induce undesirable side effects. Sulfur compounds such as sulfur and selenium disulfide representative of keratolytic agents do not show the hormone-like side effects, but often stimulate or dehydrate the skin during chronic use. Antibacterials such as hexachlorophenone, trichlorocarbanide and benzalkonium chloride show very high in vitro antimicrobial activity against the normal skin commensal, Propionibacterium acnes, but often show disappointing effects when they are actually used to treat acne in creams or ointments. Lipase inhibitors such as Ibuprofenpiconol or plant extracts such as peony or coptis root are not sufficiently effective for treating acne when they are formulated alone into creams or ointments.
A typical seborrheic disease in the scalp is increased dandruff. Excessive sebum is also considered to cause alopecia (Harada Shotaro: “Guidelines for Current Therapy, 1994 (Volume 36)”, p. 633, Igaku-Shoin, Tokyo (1994); Watanabe Yasushi et al.: “Health Science, Diagnosis List for Hair”, p. 1. Japan Hair Science Association, Tokyo (1993)). It is thought that alopecia caused by increased dandruff or excessive sebum can be treated or prevented by inhibiting sebum production.
Excessive sebum production is also known to cause cosmetic problems such as rough skin, shiny skin and greasy skin or hair.
It is known that the causative agents for increased human body odor associated with aging are also derived from sebum (Asahi Shimbun (morning edition): Aug. 30, 1999, p. 25). Any substances inhibiting sebum production may also control emission of the body odor associated with aging.
We already showed that compounds of the present invention have a platelet adhesion/aggregation suppressing effect in Japanese Patent Application No. 120425/1998 (JPA No. 310588/1999), a vascular endothelial cell growth promoting effect in Japanese Patent Application No. 273895/1998 (JPA No. 10.3738/2000) and a leukocyte-vascular endothelial cell adhesion suppressing effect in Japanese Patent Application No. 372B64/1998 (JPA No. 191538/2000). However, any sebum production inhibitory effect has not been disclosed.
As evident from the above description, it is a medically and cosmetically important object to provide an excellent sebum production inhibitor.